This study investigates the effect of natural curcuminoids on the expression of the human MDR-1 gene in multidrug-resistant human cervical carcinoma cells (KB-VI). The MDR-1 gene encodes P-glycoprotein (Pgp), a membrane protein that contributes to drug resistance by expelling drugs from cells. The researchers tested three curcuminoids—curcumin, demethoxycurcumin, and bisdemethoxycurcumin—extracted from turmeric (Curcuma longa Linn), as well as a commercial curcuminoid mixture. Western blot analysis and RT-PCR showed that all three curcuminoids inhibited MDR-1 gene expression, with bisdemethoxycurcumin being the most effective. The commercial curcuminoid mixture also reduced MDR-1 expression in a dose-dependent manner, showing similar inhibitory effects as the natural curcuminoid mixtures. These results suggest that bisdemethoxycurcumin is the most active curcuminoid in turmeric for modulating the MDR-1 gene. Treatment of drug-resistant KB-VI cells with curcumin increased their sensitivity to vinblastine, consistent with a decrease in Pgp levels on the cell membrane. This indicates that curcuminoids may act as MDR modulators by inhibiting Pgp expression. The study also highlights the potential of curcuminoids as chemosensitizing agents for cancer therapy. The findings suggest that bisdemethoxycurcumin could be a promising lead compound for developing new MDR modulators. The study provides evidence that curcuminoids can modulate MDR-1 gene expression, offering a potential therapeutic approach for overcoming drug resistance in cancer.This study investigates the effect of natural curcuminoids on the expression of the human MDR-1 gene in multidrug-resistant human cervical carcinoma cells (KB-VI). The MDR-1 gene encodes P-glycoprotein (Pgp), a membrane protein that contributes to drug resistance by expelling drugs from cells. The researchers tested three curcuminoids—curcumin, demethoxycurcumin, and bisdemethoxycurcumin—extracted from turmeric (Curcuma longa Linn), as well as a commercial curcuminoid mixture. Western blot analysis and RT-PCR showed that all three curcuminoids inhibited MDR-1 gene expression, with bisdemethoxycurcumin being the most effective. The commercial curcuminoid mixture also reduced MDR-1 expression in a dose-dependent manner, showing similar inhibitory effects as the natural curcuminoid mixtures. These results suggest that bisdemethoxycurcumin is the most active curcuminoid in turmeric for modulating the MDR-1 gene. Treatment of drug-resistant KB-VI cells with curcumin increased their sensitivity to vinblastine, consistent with a decrease in Pgp levels on the cell membrane. This indicates that curcuminoids may act as MDR modulators by inhibiting Pgp expression. The study also highlights the potential of curcuminoids as chemosensitizing agents for cancer therapy. The findings suggest that bisdemethoxycurcumin could be a promising lead compound for developing new MDR modulators. The study provides evidence that curcuminoids can modulate MDR-1 gene expression, offering a potential therapeutic approach for overcoming drug resistance in cancer.